Modification of Proteases into Peptide Ligases -Peptide ligation to native enzymes may lead to high specificity and stereoselecitivity, and may suppress side reactions. Therefore, synthesis of any enzyme that may catalyze peptide ligation will be most welcome.

Protease 'subtilisin' has been modified (by converting a serine into cysteine or seleno-cysteine) into thiol-and selenolsubtilisin, the two semi synthetic enzymes (they are damaged proteases), which can catalyse peptide ligation. Both these damaged proteases are efficient peptide ligases. Similarly histidine residue can also be modified to yield peptide ligases.